13c metabolic flux analysis identifies an unusual route for pyruvate dissimilation in mycobacteria which requires isocitrate lyase and carbon dioxide fixation

PLoS Pathogens

Volumn 7, Issue 7, 2011, Pages

  Beste, Dany J V ^a   Bonde, Bhushan ^a   Hawkins, Nathaniel ^b   Ward, Jane L ^b   Beale, Michael H ^b   Noack, Stephan ^c   Nöh, Katharina ^c   Kruger, Nicholas J ^d   Ratcliffe, R George ^d   McFadden, Johnjoe ^a  

^a UNIVERSITY OF SURREY   (United Kingdom)

^b ROTHAMSTED RESEARCH   (United Kingdom)

^c FORSCHUNGSZENTRUM JÜLICH   (Germany)

^d UNIVERSITY OF OXFORD   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO ACID; BICARBONATE; CARBON 13; CARBON DIOXIDE; GLYCEROL; GLYOXYLIC ACID; ISOCITRATE LYASE; OXALOACETIC ACID; PYRUVIC ACID; SUCCINIC ACID; SUCCINYL COENZYME A SYNTHETASE; TRICARBOXYLIC ACID; BACTERIAL PROTEIN; CARBON;

ANALYTIC METHOD; ANAPLEUROTIC REACTION; ARTICLE; BACTERIAL GROWTH; BACTERIUM CULTURE; BIOMASS; CARBON METABOLISM; CHEMICAL REACTION; CHEMOSTAT; ENZYME ACTIVITY; GENE DELETION; HOST; IN VIVO STUDY; ISOTOPE LABELING; METABOLIC FLUX ANALYSIS; MYCOBACTERIUM; NONHUMAN; OXIDATION; STEADY STATE; ENZYMOLOGY; GENETICS; HUMAN; METABOLISM; MYCOBACTERIUM BOVIS; MYCOBACTERIUM TUBERCULOSIS; PATHOGENICITY;

CORYNEBACTERINEAE; MYCOBACTERIUM BOVIS BCG; MYCOBACTERIUM TUBERCULOSIS;

BACTERIAL PROTEINS; CARBON DIOXIDE; CARBON ISOTOPES; GENE DELETION; HUMANS; ISOCITRATE LYASE; MYCOBACTERIUM BOVIS; MYCOBACTERIUM TUBERCULOSIS; PYRUVIC ACID;

EID: 79960933284     PISSN: 15537366     EISSN: 15537374     Source Type: Journal    
DOI: 10.1371/journal.ppat.1002091     Document Type: Article

References (48)

1. Beste DJV, Peters J, Hooper T, Avignone-Rossa C, Bushell ME, et al. (2005) Compiling a molecular inventory for Mycobacterium bovis BCG at two growth rates: evidence for growth rate-mediated regulation of ribosome biosynthesis and lipid metabolism. J Bacteriol 187: 1677-1684.
2. Beste DJV, Hooper T, Stewart G, Bonde B, Avignone-Rossa C, et al. (2007) GSMN-TB: a web-based genome-scale network model of Mycobacterium tuberculosis metabolism. Genome Biol 8: R89.
3. Beste DJV, Laing E, Bonde B, Avignone-Rossa C, Bushell ME, et al. (2007) Transcriptomic analysis identifies growth rate modulation as a component of the adaptation of mycobacteria to survival inside the macrophage. J Bacteriol 189: 3969-3976.
4. Beste DJV, Espasa M, Bonde B, Kierzek AM, Stewart GR, et al. (2009) The genetic requirements for fast and slow growth in mycobacteria. PLoS ONE 4: e5349.
5. McKinney JD, Honer z, Munoz E, Miczak A, Chen B, et al. (2000) Persistence of Mycobacterium tuberculosis in macrophages and mice requires the glyoxylate shunt enzyme isocitrate lyase. Nature 406: 735-738.
6. Munoz-Elias EJ, McKinney JD, (2005) Mycobacterium tuberculosis isocitrate lyases 1 and 2 are jointly required for in vivo growth and virulence. Nat Med 11: 638-644.
7. Lorenz MC, Fink GR, (2001) The glyoxylate cycle is required for fungal virulence. Nature 412: 83-86.
8. Lye YM, Chan M, Sim TS, (2005) Endorsing functionality of Burkholderia pseudomallei glyoxylate cycle genes as anti-persistence drug screens. J Mol Catal B: Enzymatic 33: 51-56.
9. Munoz-Elias EJ, Upton AM, Cherian J, McKinney JD, (2006) Role of the methylcitrate cycle in Mycobacterium tuberculosis metabolism, intracellular growth, and virulence. Mol Micro 60: 1109-1122.
10. Gengenbacher M, Rao SPS, Pethe K, Dick T, (2010) Nutrient-starved, non-replicating Mycobacterium tuberculosis requires respiration, ATP synthase and isocitrate lyase for maintenance of ATP homeostasis and viability. Microbiology 156: 81-87.
11. Baughn AD, Garforth SJ, Vilchze C, Jacobs WR, (2009) An anaerobic-type α-ketoglutarate ferredoxin oxidoreductase completes the oxidative tricarboxylic acid cycle of Mycobacterium tuberculosis. PLoS Pathog 5: e1000662.
12. Liu Z, Wang Q, Zhao X, (2008) Metabolic flux analysis of yfiD gene knockout Escherichia coli based on 13C-labeling experiments under anaerobic conditions. J Biotech 136: S34.
13. Dauner M, Storni T, Sauer U, (2001) Bacillus subtilis metabolism and energetics in carbon-limited and excess-carbon chemostat culture. J Bacteriol 183: 7308-7317.
14. Bentrup KHZ, Miczak A, Swenson DL, Russell DG, (1999) Characterization of activity and expression of isocitrate lyase in Mycobacterium avium and Mycobacterium tuberculosis. J Bacteriol 181: 7161-7167.
15. Garnier T, Eiglmeier K, Camus JC, Medina N, Mansoor H, et al. (2003) The complete genome sequence of Mycobacterium bovis. Proc Natl Acad Sci U S A 100: 7877-7882.
16. Wayne LG, Lin KY, (1982) Glyoxylate metabolism and adaptation of Mycobacterium tuberculosis to survival under anaerobic conditions. Infect Immun 37: 1042-1049.
17. Seshadri R, Suryanarayana M, Venkitasubramanian TA, (1978) Role of malic enzyme in mycobacteria: Part I-Malic enzyme & its relationship to growth rate & intracellular level of NADPH. Indian J Biochem Biophys 15: 277-281.
18. Wiechert W, Mollney M, Petersen Sr, de Graaf AA, (2001) A universal framework for 13C metabolic flux analysis. Met Eng 3: 265-283.
19. Tian J, Bryk R, Itoh M, Suematsu M, Nathan C, (2005) Variant tricarboxylic acid cycle in Mycobacterium tuberculosis: Identification of α-ketoglutarate decarboxylase. Proc Natl Acad Sci USA 102: 10670-10675.
20. de Carvalho LP, Zhao H, Dickinson CE, Arango NM, Lima CD, et al. (2010) Activity-based metabolomic profiling of enzymatic function: Identification of Rv1248c as a mycobacterial 2-hydroxy-3-oxoadipate synthase. Chem Biol 17: 323-332.
21. Prasad Maharjan R, Yu PL, Seeto S, Ferenci T, (2005) The role of isocitrate lyase and the glyoxylate cycle in Escherichia coli growing under glucose limitation. Res Micro 156: 178-183.
22. Fischer E, Sauer U, (2003) A novel metabolic cycle catalyzes glucose oxidation and anaplerosis in hungry Escherichia coli. J Biol Chem 278: 46446-46451.
23. Marrero J, Rhee KY, Schnappinger D, Pethe K, Ehrt S, (2010) Gluconeogenic carbon flow of tricarboxylic acid cycle intermediates is critical for Mycobacterium tuberculosis to establish and maintain infection. Proc Natl Acad Sci USA 107: 9819-9824.
24. Zamboni N, Maaheimo H, Szyperski T, Hohmann HP, Sauer U, (2004) The phosphoenolpyruvate carboxykinase also catalyzes C3 carboxylation at the interface of glycolysis and the TCA cycle of Bacillus subtilis. Metab Eng 6: 277-284.
25. Mukhopadhyay B, Purwantini E, (2000) Pyruvate carboxylase from Mycobacterium smegmatis: stabilization, rapid purification, molecular and biochemical characterization and regulation of the cellular level. Biochim Biophys Acta 1475: 191-206.
26. Sassetti CM, Boyd DH, Rubin EJ, (2003) Genes required for mycobacterial growth defined by high density mutagenesis. Mol Micro 48: 77-84.
27. Peters-Wendisch PG, Wendisch VF, Paul S, Eikmanns BJ, Sahm H, (1997) Pyruvate carboxylase as an anaplerotic enzyme in Corynebacterium glutamicum. Microbiology 143: 1095-1103.
28. Schaefer WB, Cohn ML, Middlebrook G, (1955) The roles of biotin and carbon dioxide in the cultivation of Mycobacterium tuberculosis. J Bacteriol 69: 706-712.
29. Nishihara H, (1954) Studies on the metabolism of the tubercule bacillus with the use of radioactive substrates in the presence and absence of streptomycin. J Biochem 41: 167-181.
30. Long ER, Anderson RJ, Rittenberg D, Karnovsky ML, Henderson HJ, (1955) The carbon metabolism of the tubercule bacillus. Am Rev Tuberc 71: 609-615.
31. Florczyk MA, McCue LA, Purkayastha A, Currenti E, Wolin MJ, et al. (2003) A family of acr-coregulated Mycobacterium tuberculosis genes shares a common DNA motif and requires rv3133c (dosR or devR) for expression. Infect Immun 71: 5332-5343.
32. Rengarajan J, Bloom BR, Rubin EJ, (2005) Genome-wide requirements for Mycobacterium tuberculosis adaptation and survival in macrophages. Proc Natl Acad Sci USA 102: 8327-8332.
33. Betts JC, Lukey PT, Robb LC, McAdam RA, Duncan K, (2002) Evaluation of a nutrient starvation model of Mycobacterium tuberculosis persistence by gene and protein expression profiling. Mol Microbiol 43: 717-731.
34. Park SW, Hwang EH, Park H, Kim JA, Heo J, et al. (2003) Growth of mycobacteria on carbon monoxide and methanol. J Bacteriol 185: 142-147.
35. Cole ST, Brosch R, Parkhill J, Garnier T, Churcher C, et al. (1998) Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature 393: 537-544.
36. Srinivasan V, Morowitz HJ, (2006) Ancient genes in contemporary persistent microbial pathogens. Biol Bull 210: 1-9.
37. Goulding CW, Bowers PM, Segelke B, Lekin T, Kim CY, et al. (2007) The structure and computational analysis of Mycobacterium tuberculosis protein CitE suggest a novel enzymatic function. J Mol Biol 365: 275-283.
38. Fregnan GB, Smith DW, Randall HM, (1961) Biological and chemical studies on mycobacteria: Relationship of colony morphology to mycoside content for Mycobacterium kansasii and Mycobacterium fortuitum. J Bacteriol 82: 517-527.
39. Lynch HC, Bushell ME, (1995) The physiology of erythromycin biosynthesis in cyclic fed batch culture. Microbiology 141: 3105-3111.
40. Sambrook J, Fritsch EF, Maniatis T, (1989) Molecular Cloning: A Laboratory Manual. Cold Spring Harbor, New York Cold Spring Harbor Laboratory Press.
41. Parish T, Stoker NG, (2000) Use of a flexible cassette method to generate a double unmarked Mycobacterium tuberculosis tlyA plcABC mutant by gene replacement. Microbiology 146: 1969-1975.
42. Mukhopadhyay B, Concar EM, Wolfe RS, (2001) A GTP-dependent vertebrate-type phosphoenolpyruvate carboxykinase from Mycobacterium smegmatis. J Biol Chem 276: 16137-16145.
43. Gourdon P, Baucher MF, Lindley ND, Guyonvarch A, (2000) Cloning of the malic enzyme gene from Corynebacterium glutamicum and role of the enzyme in lactate metabolism. Appl Environ Microbiol 66: 2981-2987.
44. Seshadri R, Suryanarayana M, Venkitasubramanian TA, (1978) Role of malic enzyme in mycobacteria: Part II-Purification & properties of malic enzyme from Mycobacterium smegmatis. Indian J Biochem Biophys 15: 282-285.
45. Wayne LG, Hayes LG, (1996) An in vitro model for sequential study of shiftdown of Mycobacterium tuberculosis through two stages of nonreplicating persistence. Infect Immun 64: 2062-2069.
46. Borodina I, Siebring J, Zhang J, Smith CP, van Keulen G, et al. (2008) Antibiotic overproduction in Streptomyces coelicolor A3(2) mediated by phosphofructokinase deletion. J Biol Chem: 283: 25186-25199.
47. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ, (1951) Protein measurement with the folin phenol reagent. J Biol Chem 193: 265-276.
48. Wiechert W, Siefke C, de Graaf AA, Marx A, (1997) Bidirectional reaction steps in metabolic networks: II. Flux estimation and statistical analysis. Biotechnol Bioeng 55: 118-135.